Abstract
IgA is the predominant Ig isotype in mucosal secretions and thus plays a pivotal role in host defense. The mechanisms by which IgA expression is regulated may differ among species and involve multiple pathways. Various cytokines and costimulators have been identified which regulate expression of this isotype, including IL-10, IL-2, vasoactive intestinal peptide, and TGF-beta. We have tested a wide array of known factors, but only under very limited conditions do these factors mediate substantial IgA production in vitro from bovine B cells. In response to these findings, we generated a cDNA library in a mammalian expression vector from activated cells derived from bovine gut-associated lymphoid tissues (Peyer's patch and mesenteric lymph node cells) as a source of soluble factor(s) that may regulate IgA production. We have identified a novel factor, IgA-inducing protein, which stimulates relatively high levels of IgA production in vitro following CD40 stimulation in coculture with IL-2. Our data suggest that IgA-inducing protein regulates IgA by acting as a switch or differentiation factor and is expressed in a variety of lymphoid and nonlymphoid tissues.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adjuvants, Immunologic / chemistry
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Adjuvants, Immunologic / genetics
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Adjuvants, Immunologic / isolation & purification
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Amino Acid Sequence
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Animals
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Antibodies, Anti-Idiotypic / pharmacology
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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Base Sequence
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CD40 Antigens / physiology
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COS Cells
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Cattle
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Cells, Cultured
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Clone Cells
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DNA, Complementary / isolation & purification
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GTP Phosphohydrolases / biosynthesis*
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GTP Phosphohydrolases / genetics
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GTP Phosphohydrolases / isolation & purification
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GTP Phosphohydrolases / metabolism
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Gene Library
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Humans
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Immunoglobulin A / biosynthesis*
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Immunoglobulin M / immunology
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Intestinal Mucosa / chemistry
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Leukocytes / immunology
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Leukocytes / metabolism
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Lymphoid Tissue / chemistry
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Lymphoid Tissue / immunology
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Lymphoid Tissue / metabolism
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Mice
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Molecular Sequence Data
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Nuclear Proteins / biosynthesis*
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Nuclear Proteins / genetics
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Nuclear Proteins / isolation & purification
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Nuclear Proteins / metabolism
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Organ Specificity
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Proteins / chemistry*
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Proteins / genetics
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Proteins / isolation & purification*
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Recombinant Proteins / pharmacology
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Transcription, Genetic
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Transforming Growth Factor beta / pharmacology
Substances
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Adjuvants, Immunologic
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Antibodies, Anti-Idiotypic
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CD40 Antigens
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DNA, Complementary
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Immunoglobulin A
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Immunoglobulin M
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Nuclear Proteins
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Proteins
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Recombinant Proteins
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Transforming Growth Factor beta
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anti-IgM
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GTP Phosphohydrolases
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GVINP1 protein, human